Simultaneous pancreas-kidney (SPK) transplantation is currently considered the preferred therapeutic option in beta-cell-penic diabetic patients with end-stage renal failure. Refinements in surgical techniques and postoperative care, implementation of antimicrobial and antiviral prophylaxis protocols, and availability of more effective immunosuppression regimens have all contributed to the current success of SPK. Patient and graft survival rate for primary SPK now exceed 95 and 85 %, respectively. The half-life of pancreas graft averages 16.7 years, achieving the longest duration found among extrarenal grafts. With more patients enjoying technically successful SPK, newer issues are emerging in the follow-up period, such as the impact of de novo donor-specific HLA antibodies and reactivation of autoimmunity. Because of the ageing of brain-dead donors, donor shortage is the main factor currently limiting the feasibility of SPK. Live donor kidney transplantation, possibly followed by pancreas after kidney transplantation, is an alternative approach which seems to be equally effective despite requiring two surgical operations. Donation after cardiac death is an additional possibility, but it is not evenly feasible in all countries because of different legislation.